title: Inhibition of HIV-1 infection in vitro by monoclonal antibodies to the complement receptor type 3 (CR3): an accessory role for CR3 during virus entry?
abstract: Adhesion molecules are known to contribute to infectivity of HIV-1. Here we tested whether the complement receptor type 3 (CR3, CD11b), an alpha(m)beta2 integrin, plays an accessory role in the infection process of HIV-1, because ICAM-1, a ligand of CR3, is present on the envelope of HIV-1. In addition, the viral transmembrane protein gp41 shares four regions of homology with the complement component C3, a further CR3 ligand. Infection of PBMCs with HIV-IIIB and primary isolates was partially inhibited by anti-CR3 antibodies. A peptide derived from the complement component C3, covering the CR3-binding site of C3 and sharing strong similarity to the immunosuppressive region of gp41, significantly reduced the HIV-1 titer in infection assays. Recombinant soluble gp41 (rsgp41) and the peptide covering the immunosuppressive domain of gp41 inhibited the rosetting of iC3b-coated sheep erythrocytes with U937 via complement receptors (CRs) with an efficiency comparable to monoclonal anti-CR antibodies. In addition, sub-populations of CD4 + and CD8 + T-cells isolated from HIV-infected individuals were found to upregulate CR3 as determined by FACS analysis and on the mRNA level. Since gp41 has been implicated in viral fusion, an interaction of its C3-homology region in gp41 or an interaction of ICAM on the surface of free virus with CRs might contribute to facilitate viral entry.
authors.affiliation: Institut für Hygiene and Ludwig Boltzmann Institut für AIDS-Forschung, Innsbruck, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Stoiber
authors.forename: I
authors.initials: I
authors.lastname: Frank
authors.forename: M
authors.initials: M
authors.lastname: Spruth
authors.forename: M
authors.initials: M
authors.lastname: Schwendinger
authors.forename: B
authors.initials: B
authors.lastname: Mullauer
authors.forename: J M
authors.initials: JM
authors.lastname: Windisch
authors.forename: R
authors.initials: R
authors.lastname: Schneider
authors.forename: H
authors.initials: H
authors.lastname: Katinger
authors.forename: I
authors.initials: I
authors.lastname: Ando
authors.forename: M P
authors.initials: MP
authors.lastname: Dierich
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002469:Cell Separation; D005434:Flow Cytometry; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000378:metabolism / Q000472:pathogenicity; D006801:Humans; D007116:Immunization, Passive; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008565:Membrane Proteins; D012333:RNA, Messenger / Q000032:analysis; D011951:Receptors, Complement / Q000235:genetics / Q000276:immunology*; D012397:Rosette Formation
chemical_list: D019380:Anti-HIV Agents; D000911:Antibodies, Monoclonal; D016177:Macrophage-1 Antigen; D008565:Membrane Proteins; D012333:RNA, Messenger; D011951:Receptors, Complement; C085567:complement C3a receptor